title: The postprandial rise in plasma cortisol in men is mediated by macronutrient-specific stimulation of adrenal and extra-adrenal cortisol production.
abstract: BACKGROUND
  Circadian variation is a fundamental characteristic of plasma glucocorticoids, with a postprandial rise in cortisol an important feature. The diurnal rhythm is presumed to reflect alterations in hypothalamic-pituitary-adrenal axis activity; however, cortisol is produced not only by the adrenal glands but also by regeneration from cortisone by the enzyme 11β-hydroxysteroid dehydrogenase type 1, mainly in liver and adipose tissue.
  
  
  OBJECTIVE
  We tested the contribution of peripheral cortisol regeneration to macronutrient-induced circadian variation of plasma cortisol in humans.
  
  
  METHODS
  This was a randomized, single-blinded, crossover study.
  
  
  METHODS
  The study was conducted at a hospital research facility.
  
  
  METHODS
  Eight normal-weight healthy men participated in the study.
  
  
  METHODS
  Subjects were given isocaloric energy isodense flavor-matched liquid meals composed of carbohydrate, protein, fat, or low-calorie placebo during infusion of the stable isotope tracer 9,11,12,12-[2H]4-cortisol.
  
  
  RESULTS
  Plasma cortisol increased similarly after all macronutrient meals (by ∼90 nmol/L) compared with placebo. Carbohydrate stimulated adrenal secretion and extra-adrenal regeneration of cortisol to a similar degree. Protein and fat meals stimulated adrenal cortisol secretion to a greater degree than extra-adrenal cortisol regeneration. The increase in cortisol production by 11β-hydroxysteroid dehydrogenase type 1 was in proportion to the increase in insulin. The postprandial cortisol rise was not accounted for by decreased cortisol clearance.
  
  
  CONCLUSIONS
  Food-induced circadian variation in plasma cortisol is mediated by adrenal secretion and extra-adrenal regeneration of cortisol. Given that the latter has the more potent effect on tissue cortisol concentrations and that effects on adrenal and extra-adrenal cortisol production are macronutrient specific, this novel mechanism may contribute to the physiological interplay between insulin and glucocorticoids and the contrasting effects of certain diets on postprandial metabolism.
authors.affiliation: University/British Heart Foundation Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom.
authors.forename: Roland H
authors.initials: RH
authors.lastname: Stimson
authors.affiliation: University/British Heart Foundation Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom.
authors.forename: Nor A
authors.initials: NA
authors.lastname: Mohd-Shukri
authors.affiliation: University/British Heart Foundation Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Bolton
authors.affiliation: University/British Heart Foundation Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom.
authors.forename: Ruth
authors.initials: R
authors.lastname: Andrew
authors.affiliation: University/British Heart Foundation Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom.
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Reynolds
authors.affiliation: University/British Heart Foundation Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom.
authors.forename: Brian R
authors.initials: BR
authors.lastname: Walker
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000311:Adrenal Glands / Q000378:metabolism*; D000328:Adult; D018592:Cross-Over Studies; D004435:Eating / Q000502:physiology*; D005502:Food; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D010913:Pituitary-Adrenal System / Q000378:metabolism; D010919:Placebos; D019518:Postprandial Period; D016037:Single-Blind Method; D055815:Young Adult
chemical_list: D010919:Placebos; D006854:Hydrocortisone